Advanced age is associated with a reduced ability of tissue to respond to adrenergic agonists. This appears to be due to an age-related reduction in the number of adrenergic receptors in these tissues. Our finding that certain areas of the central nervous system from aged rats fail to produce a denervation supersensitivity in response to decreased adrenergic input suggests this reduction of adrenergic receptors may be caused by an inability of these tissues to alter their number of adrenergic receptors in response to changing internal and external stimuli. In this proposal we plan to study the mechanism for this defect in cellular communication by determinig the neural and hormonal factors that influence alpha- and beta-adrenergic receptors and by determining the influence of age on the ability of tissue to respond to these factors. Two model systems will be studied: Using the rat pineal gland maintained in organ culture, we plan to determine the rate of synthesis of adrenergic receptors in pineal gland of rats of different ages. We also plan to study whether age influences the capacity of hormones to alter the number and synthesis of adrenergic receptors. These studies may uncover the defect in aging that is responsible for the reduced ability of aged individuals to maintain homeostasis in response to stress. A second model system we will study is the hypothalamic-pituitary-ovarian axis in the rat. In advanced age ovarian hormones no longer can regulate the secretion of gonadotropins. We will study whether this defect may also be due to a decreased ability of the aged rat to regulate the adrenergic receptors in specific regions of the hypothalamus, regions that are responsible for controlling gonadotropin secretion. Information on the mechanisms responsible for the age-related reduction in adrenergic receptors in brain may suggest a neuropharmacological approach toward preventing those changes.